Immunoglobulins conjugated to a drug of interest, generally known as antibody drug conjugates (ADCs), are a promising area of therapeutic research. Recent developments in ADC technology have focused on linker technology that provides for intracellular cleavage or more recently, non-cleavable linkers that provide greater in vivo stability and reduced toxicity. The feasibility of an ADC approach, however, is not only depend on linker technologies and drugs, but also on the cellular target, and moreover upon the particular antibody to which a drug is linked. Antibodies may bind antigens in different ways, e.g. giving rise to different profiles of internalization, or antibodies may bind to epitopes present on non-targeted tissues. As a consequence, it is generally believed that each antibody must be examined separately. Evaluating large numbers of antibodies for their suitability for ADC approaches is difficult because antibodies must be conjugated to drugs in a stoichiometric manner such that the effect of the antibody (e.g. epitope specificity, affinity, etc.) can be separated from the effect of the drug. Screening of antibodies suitable for further development as ADCs therefore remains an expensive and time-consuming process.
In view of the foregoing, there remains a need in the art for methods to assess which combination of antibody, linker and drug structure are best suited for a particular application.